Ventilator-associated Tracheobronchitis Research Articles

A Bibliometric Analysis of the Role and Research Trending of Bronchoalveolar Lavage in the Diagnosis and Treatment of Ventilator-Associated Pneumonia.

Ventilator-associated pneumonia (VAP) is one of the most common complications in intensive care units (ICUs) and negatively affects patient outcomes. Despite its widespread use as a diagnostic and therapeutic measure, the application and effectiveness of bronchoalveolar lavage (BAL) in the management of VAP require further exploration. This study aimed to evaluate the research dynamics, major trends, and scientific networks of BAL in the diagnosis and treatment of VAP using bibliometric analysis. Literature from the Web of Science database on BAL for the diagnosis and treatment of VAP from 1990 to 2024 was screened and analyzed. Keyword co-occurrence, trend analysis, and citation burst analyses were conducted using CiteSpace to identify research hotspots, core authors, institutions, and countries, as well as the evolution of research domains. The bibliometric analysis included 968 publications. Trend analysis indicated growing interest in BAL techniques, particularly in the categories of RESPIRATORY SYSTEM (burst score: 27.82) and MEDICINE, RESEARCH, and EXPERIMENTAL (burst score: 7.41). The co-citation analysis highlighted influential authors in the field, such as Torres(burst score: 9.35), Croce (burst score: 5.86), and Meduri(burst score: 5.71). Keyword analysis results revealed core clusters in the treatment of VAP with BAL, including "nonbronchoscopic lavage" (silhouette value: 0.703), "ICU-acquired infection" (silhouette value: 0.7), and "ventilator-associated tracheobronchitis" (silhouette value: 0.637). Additionally, geographic analysis showed that North America and Europe dominated the research in this field. Recently, research trends regarding protected specimen brushes and quantitative culture techniques have emerged. This study found broad applications of BAL in VAP management, especially in improving diagnostic accuracy and treatment outcomes. Optimized strategies such as improvement of lavage techniques and multidisciplinary collaboration may emerge as potential research hotspots in the future.

A prospective study on clinical profile, severity, microbiology, and outcome of patients with ventilator associated infective complications admitted in intensive care unit of a tertiary care hospital

: Mechanical ventilation epitomizes intensive care medicine. Ventilator‑associated complications are mainly Ventilator associated respiratory infections (VARI); These are a major cause of concern in the intensive care units (ICUs) worldwide, especially in developing countries. VARI includes patients with ventilator‑associated tracheobronchitis (VAT) and ventilator‑associated pneumonia (VAP).The clinical profile, severity, microbiology, and outcomes of such infections is not well described in Eastern India. The primary objective of the study was to study the risk factors, severity scoring, microbiological profile and 28 days outcome of patients admitted in intensive care unit of our hospital.Secondary objective of our study was to find out any correlation between risk factors, severity scoring, microbiological profile, and outcome of patients with VAT and VAP admitted in intensive care unit of our hospital.: This was a prospective observational study done in the ICU of a tertiary care centre in eastern India. A total 50 patients of clinically, microbiologically and/or radiologically diagnosed case of VAP and VAT were included in the study. A structured data collection proforma was prepared and data collection was done. Raw data was tabulated and analysed: 66% of our patients were male, Smoking was the commonest addiction(24%), VARI developed early with 17% on Day 3, 72% developed VARI within 5 days of ventilation. 16% had history of recent admission, Diabetes and hypertension were the commonest comorbidities. 58% of the patients developed VAP, the median SOFA score in VAP was 6 also similar in VAT. Patients with neurological diseases had the maximum number of VAT and VAP. Klebsiella pneumoniae was the commonest organism causing VAT (42%) while Acinetobacter Baumanii was commonest to cause VAP (44%). 51% of VAP patients were on volume control mode, while it was 52% of VAT patients. Most isolates are MDR pathogens with intermediate sensitivity to Polymyxin being most common (66%) 1 isolate was pan resistant. Mortality was 58% for VAP and 19% in VAT. Both Klebsiella and Acinetobacter accounts for 41% death in VAP group, in VAT group Klebsiella was commonest however no statistical significance with other organism.: Gram negative bacteria were the predominant cause of VAT and VAP, Acinetobacter and Klebsiella are the commonest organisms. Most Isolates are MDR with intermediate sensitivity to Polymyxins. Median SOFA scores were the same in both. Mortality was high in VAP group. Volume control mode was predominant mode of ventilation, Neurological causes was predominant cause that leads to ventilation and subsequent VARI.

Outcomes associated with ventilator-associated events (VAE), respiratory infections (VARI), pneumonia (VAP) and tracheobronchitis (VAT) in ventilated pediatric ICU patients: A multicentre prospective cohort study

ObjectivesAn objective categorization of respiratory infections based on outcomes is an unmet clinical need. Ventilator-associated pneumonia and tracheobronchitis remain used in clinical practice, whereas ventilator-associated events (VAE) are limited to surveillance purposes. Research methodology/designThis was a secondary analysis from a multicentre observational prospective cohort study. VAE were defined as a sustained increase in minimum Oxygen inspired fraction (FiO2) and/or Positive end-expiratory pressures (PEEP) of ≥ 0.2/2 cm H2O respectively, or an increase of 0.15 FiO2 + 1 cm H20 positive end-expiratory pressures for ≥ 1 calendar-day. Setting15 Paediatric Intensive Care Units. Main outcome measuresMechanical ventilation duration, intensive care and hospital length of stay; (LOS) and mortality. ResultsA cohort of 391 ventilated children with an age (median, [Interquartile Ranges]) of 1 year[0.2–5.3] and 7 days[5–10] of mechanical ventilation were included. Intensive care and hospital stays were 11 [7–19] and 21 [14–39] days, respectively. Mortality was 5.9 %. Fifty-eight ventilator-associated respiratory infections were documented among 57 patients: Seventeen (29.3 %) qualified as ventilator-associated pneumonia (VAP) and 41 (70.7 %) as ventilator-associated tracheobronchitis (VAT). Eight pneumonias and 16 tracheobronchitis (47 % vs 39 %,P = 0.571) required positive end-expiratory pressure or oxygen increases consistent with ventilator-associated criteria. Pneumonias did not significantly impact on outcomes when compared to tracheobronchitis. In contrast, infections (pneumonia or tracheobronchitis) following VAEs criteria were associated with > 6, 8 and 15 extra-days of ventilation (16 vs 9.5, P = 0.001), intensive care stay (23.5 vs 15; P = 0.004) and hospital stay (39 vs 24; P = 0.015), respectively. ConclusionWhen assessing ventilated children with respiratory infections, VAE apparently is associated with higher ventilator-dependency and LOS compared with pneumonia or tracheobronchitis. Implications for practiceIncorporating the modification of ventilatory settings for further categorization of the respiratory infections may facilitate therapeutic management among ventilated patients.

Ventilator-Associated Lower Respiratory Tract Infections and Their Association With COVID-19: A Retrospective Cohort Study in a Portuguese Intensive Treatment Unit.

Introduction Ventilator-associated pneumonia (VAP) is the most common infectious complication related to admission to an Intensive Treatment Unit (ITU). Ventilator-associated lower respiratory tract infection (VA-LRTI) is a broader diagnosis than VAP. By disregarding radiological criteria, it will include both VAP and ventilator-associated tracheobronchitis. This study,conducted in the setting of a Portuguese ITU, aims to study the incidence, microbiology and clinical outcome of VA-LRTI and its association with COVID-19. Methods A retrospective cohort study included patients admitted to a Portuguese ITU who underwent invasive mechanical ventilation (IMV) for over 48 hours between 01/01/2021 and 31/12/2021. The Hospitals in Europe Link for Infection Control through Surveillance (HELICS) criteria were applied, disregarding the radiological criteria, for the diagnosis of VA-LRTI. Results The group of patients with COVID-19 had 46.38 episodes of VA-LRTI/1000 days of ventilation, while patients without COVID-19 had 16.35 episodes/1000 days of ventilation (RR 2.78, p < 0.001). Of the 85 microorganisms isolated, 82% were gram-negative microorganisms, with species of the genus Klebsiella being the most prevalent (22.4%). There was a lower prevalence of beta-lactam-resistant organisms in patients with COVID-19 (RR 0.35, p = 0.031). The development of VA-LRTI is associated with longer times ofIMV (difference in medians 10 days, p < 0.001), but with no significant differences in mortality (RR 1.21, p = 0.14). Discussion Patients with COVID-19 seem more predisposed to developing VA-LRTI, possibly due to intrinsic characteristics of the disease. Although no increase in mortality has been demonstrated, VA-LRTI can entail important costs related to morbidity, antibiotic pressure and economic costs that must be considered.

Protein-energy malnutrition prevalence and influence on complications and outcome of severe stroke, requiring mechanical ventilation: a multicenter prospective observational trial

INTRODUCTION: Stroke is characterized by high prevalence and mortality. Protein-energy deficiency is a common syndrome in this category of patients, affecting the course and outcomes of cerebral stroke. OBJECTIVE: The purpose of the study was to analyze the prevalence and impact on the course and outcome of stroke of protein-energy deficiency in patients with mechanical ventilation. MATERIALS AND METHODS: A multicenter observational clinical study “Register of respiratory therapy in patients with stroke (RETAS)” was conducted under the auspices of the Russian Federation of Anesthesiologists and Reanimatologists. The study involved 14 centers, included 1289 acute stroke patients received respiratory support. RESULTS: Protein-energy deficiency in patients with stroke on mechanical ventilation was associated with a tendency to a greater risk of a lethal outcome (p = 0.0003). The absence of protein-energy malnutrition in patients with stroke severity less than 14 points during mechanical ventilation was associated with a greater likelihood of a positive outcome (Glasgow Outcome Scale, GOS 4 and 5) compared with patients with signs of malnutrition (p = 0.000002). Protein-energy malnutrition is associated with prolonged stay in ICU of patients with stroke on mechanical ventilation (p &lt; 0.0001). At the same time, the group of patients with prolonged mechanical ventilation was characterized by a high prevalence of bedsores (p &lt; 0.0001), hypoproteinemia, hypoalbuminemia (р = 0.0001), and decreased body weight 10 percent or more (p &lt; 0.0001). The presence of protein-energy malnutrition was accompanied by an increased risk of ventilator-associated tracheobronchitis in patients with stroke (p &lt; 0.0001). CONCLUSIONS: Protein-energy malnutrition significantly influences on the course and clinical outcome parameters of severe cerebral stroke patients on mechanical ventilation.

ICU-acquired infections in immunocompromised patients.

Immunocompromised patients account for an increasing proportion of the typical intensive care unit (ICU) case-mix. Because of the increased availability of new drugs for cancer and auto-immune diseases, and improvement in the care of the most severely immunocompromised ICU patients (including those with hematologic malignancies), critically ill immunocompromised patients form a highly heterogeneous patient population. Furthermore, a large number of ICU patients with no apparent immunosuppression also harbor underlying conditions altering their immune response, or develop ICU-acquired immune deficiencies as a result of sepsis, trauma or major surgery. While infections are associated with significant morbidity and mortality in immunocompromised critically ill patients, little specific data are available on the incidence, microbiology, management and outcomes of ICU-acquired infections in this population. As a result, immunocompromised patients are usually excluded from trials and guidelines on the management of ICU-acquired infections. The most common ICU-acquired infections in immunocompromised patients are ventilator-associated lower respiratory tract infections (which include ventilator-associated pneumonia and tracheobronchitis) and bloodstream infections. Recently, several large observational studies have shed light on some of the epidemiological specificities of these infections-as well as on the dynamics of colonization and infection with multidrug-resistant bacteria-in these patients, and these will be discussed in this review. Immunocompromised patients are also at higher risk than non-immunocompromised hosts of fungal and viral infections, and the diagnostic and therapeutic management of these infections will be covered. Finally, we will suggest some important areas of future investigation.

VATICAN (Ventilator-Associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation): protocol for a multicenter randomized open-label trial of watchful waiting versus antimicrobial therapy for ventilator-associated tracheobronchitis.

Ventilator-associated tracheobronchitis is a common condition among invasively ventilated patients in intensive care units, for which the best treatment strategy is currently unknown. We designed the VATICAN (Ventilator-Associated Tracheobronchitis Initiative to Conduct Antibiotic Evaluation) trial to assess whether a watchful waiting antibiotic treatment strategy is noninferior to routine antibiotic treatment for ventilator-associated tracheobronchitis regarding days free of mechanical ventilation. VATICAN is a randomized, controlled, open-label, multicenter noninferiority trial. Patients with suspected ventilator-associated tracheobronchitis without evidence of ventilator-associated pneumonia or hemodynamic instability due to probable infection will be assigned to either a watchful waiting strategy, without antimicrobial administration for ventilator-associated tracheobronchitis and prescription of antimicrobials only in cases of ventilator-associated pneumonia, sepsis or septic shock, or another infectious diagnosis, or to a routine antimicrobial treatment strategy for seven days. The primary outcome will be mechanical ventilation-free days at 28 days, and a key secondary outcome will be ventilator-associated pneumonia-free survival. Through an intention-to-treat framework with a per-protocol sensitivity analysis, the primary outcome analysis will address noninferiority with a 20% margin, which translates to a 1.5 difference in ventilator-free days. Other analyses will follow a superiority analysis framework. The VATICAN trial will follow all national and international ethical standards. We aim to publish the trial in a high-visibility general journal and present it at critical care and infectious disease conferences for dissemination. These results will likely be immediately applicable to the bedside upon trial completion and will provide information with a low risk of bias for guideline development.

Ventilator-associated tracheobronchitis (VAT ) - systematic review

Ventilator-associated tracheobronchitis (VAT), along with the relatively well-studied ventilator-associated pneumonia (VAP), form the ventilator-associated lower respiratory tract inflammation (VA-LRTI ) disease group, which is undoubtedly a significant challenge for Intensive care units (ICUs) staff caring for mechanically ventilated patients daily. Recently, the topic of VAT has been increasingly addressed and researched to better understand and comprehend this disease unit. Despite its still uncertain definition, VAT is recognized as a disease entity independent of VAP, considered by many researchers to be either an intermediate stage or a risk factor for faster progression of VAP. Based on the available literature and the experience of the authors, we have selected 31 articles published between 2004 and 2023 that are both research and review papers in order to systematise the basic information and diagnosis of VAT, as well as to show the complexity of the problem, which is the issue of treatment and co-occurrence of VAT in critical patients as well as complicated by other respiratory diseases. It is hoped that this review will allow will enable medical personnel, especially those who work on a daily basis with patients undergoing mechanical ventilation, to look at VAT from a different angle and encourage further research to understand it better.

Artificial ventilation in patients with stroke: main results of the Russian multicenter observational clinical trial RETAS

To analyze the relationship between the characteristics of respiratory support (RS) for patients with stroke and clinical factors with the number and structure of complications, deaths, and length of stay in the intensive care unit (ICU) and duration of artificial pulmonary ventilation (ALV). The Russian multicenter observational clinical study «Respiratory Therapy for Acute Stroke» (RETAS) that enrolled 1289 patients with stroke requiring RS was conducted under the auspices of the All-Russian public organization «Federation of Anesthesiologists and Resuscitators». Indications for ALV, the use of hyperventilation, the maximum level of positive end-expiratory pressure, starting modes of mechanical ventilation, timing of tracheostomy, the incidence of protein-energy malnutrition (PEM) and infectious complications were analyzed. The following scales were used to assess the severity of the condition: the National Institutes of Health Stroke Severity Scale (NIHSS), the Glasgow Coma Scale, the Glasgow Outcome Scale (GOS). For the group of patients with a stroke severity of more than 20 NIHSS points, the mortality increase was associated with initial hypoxia (p=0.004), hyperventilation used to relieve intracranial hypertension (p=0.034), and starting ventilation with volume control (VC) compared with starting pressure-controlled ventilation (PC) (p<0.001). We found that the use of the instrumental monitoring of intracranial pressure was associated with a decrease in mortality (p<0.001). The absence of PEM in patients with stroke is associated with a higher probability of a positive outcome (GOS 4 and 5) for the group with NIHSS less than 14 points (p<0.001). Ventilator-associated tracheobronchitis and ventilator-associated pneumonia were associated with an increase in the duration of ALV, the duration of weaning from the ventilator (for ventilator-associated tracheobronchitis) and the duration of stay in the ICU, and also reduced the chances of favorable outcomes (p<0.05). The factors associated with increased mortality in acute stroke are: hypoxemia at the start of ALV, hyperventilation, starting ventilation with VC in comparison with starting ventilation with PC, the use of only clinical methods of monitoring intracranial pressure in comparison with instrumental monitoring. The adverse effect of PEM and infectious complications on the outcome in patients with acute stroke has been proven.

Epidemiology of ventilator-associated tracheobronchitis and ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria at a tertiary care hospital in Thailand.

To investigate the epidemiology of MDR Gram-negative bacilli ventilator-associated tracheobronchitis (MDR GNB-VAT) and MDR GNB ventilator-associated pneumonia (MDR GNB-VAP) among mechanically ventilated patients. We conducted a retrospective observational study among hospitalized patients who underwent continuous mechanical ventilation for ≥48 h at Siriraj Hospital, Thailand. During the 18 month study period, 1824 unique patients underwent continuous mechanical ventilation (12 216 ventilator-days). The cumulative incidences of MDR GNB-VAT and -VAP were 8.4% and 8.3%, respectively. The incidence rates of MDR GNB-VAT and -VAP were 12.52 and 12.44 episodes/1000 ventilator-days, respectively. Among those with VAT, the cumulative incidence and incidence rate of subsequent VAP development within 7 days were 11.76% and 2.81 episodes/1000 ventilator-days, respectively. The median durations of mechanical ventilation before having VAP and VAT were 9 and 12 days, respectively. Multivariate analysis identified three independently associated factors for patients having VAP compared with having VAT: underlying cerebrovascular disease [adjusted OR (aOR): 0.46; 95% CI: 0.27-0.78; P = 0.04], previous surgery (aOR: 0.68; 95% CI: 0.57-0.8; P < 0.001) and acute renal failure (aOR: 1.75; 95% CI: 1.27-2.40; P = 0.001). The study revealed high incidences of MDR GNB-VAT and -VAP among mechanically ventilated patients. The independent risk factors for having VAP can help identify patients at risk for developing VAP and who need early weaning from mechanical ventilation.

European Network for ICU-Related Respiratory Infections (ENIRRIs): a multinational, prospective, cohort study of nosocomial LRTI

PurposeLower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes.MethodsA prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups.Results1060 patients with LRTI (72.5% male sex, median age 64 [50–74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates.ConclusionVHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study.

Morphometric and microbiological features of ventilator associated tracheobronchitis

Changes in the composition of the microbiota of the tracheobronchial tree in patients on prolonged mechanical ventilation can contribute to various disorders of the immune defense of the respiratory tract, damaging mucociliary clearance, and cause a strong inflammatory response, including the formation of ventilator-associated tracheobronchitis (VAT). The aim was to study the specifics of changes in the microflora and histopathology of the tracheobronchial tree in VAT. Over a 10 year period 975 bacteriological analyzes were carried out in 355 patients who were on extended mechanical ventilation for more than 48 hours. VAT is accompanied by a pronounced lymphoid-neutrophilic infiltration of the mucosa of the trachea and bronchi, and in a complicated course with the presence of a purulent-inflammatory and erosive-hemorrhagic component leads to a violation of the integrity of tissues due to destruction and necrosis. The leading pathogens were representatives of gram-negative flora of 65.8% (47-76%), gram-positive flora was detected in 17.5% (10-30%) of cases, fungi of the genus Candida in 16.5 (4-42%) cases. Analysis of the antibiograms of isolated cultures in patients on prolonged mechanical ventilation shows high resistance to a wide range of antibiotics, namely: acinetobacter spp. - high resistance to all antibiotics, except for imipenem (0% resistant strains), polymyxin (0%) and tetracyclines (7-15.4%). Imipenem (10.5%), polymyxin (10.5%), amikacin (31.5%) and cefoperazone/sulbactam (31.5%) are active against Esherichia coli. Klebsiella pneumoniae was susceptible to imipenem, amikacin, ofloxacin and inhibitor-protected antibiotics-cefoperazone/sulbactam, piperacillin/tazobactam. Staphylococcus aureus was susceptible to III generation cephalosporins (cefotaxime, ceftriaxone, cefoperazone) and tetracyclines - 36.3% of resistant strains. Microbiological monitoring in patients with VAT over a 10-year period revealed a trend towards the prevalence of gram-negative microflora inoculation, and over the past two years, the range of isolated multi-resistant flora has been expanding.

Morphometric and microbiological features of ventilator associated tracheobronchitis

Changes in the composition of the microbiota of the tracheobronchial tree in patients on prolonged mechanical ventilation can contribute to various disorders of the immune defense of the respiratory tract, damaging mucociliary clearance, and cause a strong inflammatory response, including the formation of ventilator-associated tracheobronchitis (VAT). The aim was to study the specifics of changes in the microflora and histopathology of the tracheobronchial tree in VAT. Over a 10 year period 975 bacteriological analyzes were carried out in 355 patients who were on extended mechanical ventilation for more than 48 hours. VAT is accompanied by a pronounced lymphoid-neutrophilic infiltration of the mucosa of the trachea and bronchi, and in a complicated course with the presence of a purulent-inflammatory and erosive-hemorrhagic component leads to a violation of the integrity of tissues due to destruction and necrosis. The leading pathogens were representatives of gram-negative flora of 65.8% (47-76%), gram-positive flora was detected in 17.5% (10-30%) of cases, fungi of the genus Candida in 16.5 (4-42%) cases. Analysis of the antibiograms of isolated cultures in patients on prolonged mechanical ventilation shows high resistance to a wide range of antibiotics, namely: acinetobacter spp. - high resistance to all antibiotics, except for imipenem (0% resistant strains), polymyxin (0%) and tetracyclines (7-15.4%). Imipenem (10.5%), polymyxin (10.5%), amikacin (31.5%) and cefoperazone/sulbactam (31.5%) are active against Esherichia coli. Klebsiella pneumoniae was susceptible to imipenem, amikacin, ofloxacin and inhibitor-protected antibiotics-cefoperazone/sulbactam, piperacillin/tazobactam. Staphylococcus aureus was susceptible to III generation cephalosporins (cefotaxime, ceftriaxone, cefoperazone) and tetracyclines - 36.3% of resistant strains. Microbiological monitoring in patients with VAT over a 10-year period revealed a trend towards the prevalence of gram-negative microflora inoculation, and over the past two years, the range of isolated multi-resistant flora has been expanding.

Transcriptomics reveals shared immunosuppressive landscapes in ventilator-associated lower respiratory tract infections (VA-LRTI) patients

ABSTRACT Background Ventilator-associated pneumonia (VAP) represents a transitory status of immunoparalysis, and we hypothesized that ventilator-associated tracheobronchitis (VAT) could share also some degree of immune response to a respiratory infection. Research design and methods A prospective observational study in five medical ICUs to evaluate immunological alterations of patients with VA-LRTI. Immunological gene expression profiles in the blood using whole transcriptome microarrays in the first 24 hours following diagnosis. The area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of mRNA levels to differentiate VA-LRTI and lack of infection. A principal component analysis (PCA) was employed for analyzing the impact of each genetic expression footprint variable in explaining the variance of the cohort. Results There was overlapping between the three classes of patients encompassing gene expression levels of 8 genes (i.e. HLA, IL2RA, CD40LG, ICOS, CCR7, CD1C, CD3E). HLA-DRA was equally low among VAT and VAP patients characterizing immune depression, and significantly lower than the control group. Conclusions Our findings suggest that VAP and VAT are not so different regarding gene expression levels suggesting a degree of immunosuppression. Our results indicate a state of immunoparalysis in respiratory infections in critically ill patients.

Impact of multizonal decontamination of upper respiratory tract on incidence of ventilator-associated pneumonia: multicenter randomized pilot study

INTRODUCTION: Ventilator-associated pneumonia (VAP) is the one of nosocomial infections in intensive care units. VAP can result in prolonged duration of hospitalization and invasive mechanical ventilation (MV) that is associated with attributive mortality. OBJECTIVE: The aim of our pilot multicenter randomized study was to assess effect of the multizonal decontamination of upper airway including subglottic space on the VAP incidence and time of onset, as well as colonization upper airway and clinical outcomes. MATERIALS AND METHODS: Sixty patients requiring the prolonged MV were included in the prospective study. All participants were randomized into three groups: the control, the local antiseptic (LA) and the bacteriophage (BP). All patients were managed using similar VAP protective bundle. Infection-related ventilator-associated complications (IVAC) were registered based on clinical, laboratory, and instrumental examination. Diagnosis of VAP was confirmed if CPIS was ≥ 6 points. RESULTS: A total incidence of IVAC did nоt differ between groups: 15 (75 %), 14 (70 %), and 17 (85 %) cases in the control, LA, and BP groups, respectively. The VAP incidence was lower in the LA and BP groups compared with the controls: 3 (15 %) and 3 (15 %) vs 10 (50 %) cases (χ2 = 8.35; p = 0.015). The overall mortality was 30 % and did not differ between the groups. Multi-selective decontamination resulted in a trend to increased ventilator-associated tracheobronchitis incidence in the BP group and to silent colonization in both LA and BP groups (p = 0.07). No differences in the duration of MV, ICU and hospital stay were observed. CONCLUSIONS: The combined multizonal upper airway decontamination involving subglottic space is associated with a reduction of the VAP incidence but did not change the overall IVAC rate. Multizonal decontamination based on subglottic bacteriophage instillation might have a potential to influence the microbial heterogeneity of upper airways.

A proposed new method of hemostasis for erosive-hemorrhagic complications of the trachea and bronchi

Ventilator-associated complications are the most frequent ones that prevent the recovery of intensive care patients. This study aimed to evaluate the effectiveness of the endoscopic treatment of acute hemorrhagic lesions of the tracheobronchial tree in patients with ventilator-associated tracheobronchitis. A total of 5 patients (22.4±3.3 mean age, 18 to 36 years) with prolonged mechanical ventilation (&gt;48 hours) in the resuscitation and intensive care unit were monitored. The diagnosis of ventilator-associated tracheobronchitis was established on the basis of clinical signs, radiological and microbiological criteria. Fine-dispersed powder with hemostatic properties (HEMOBEN) was used as a hemostatic agent when applying the method. A morphometric study noted that ventilator-associated tracheobronchitis is accompanied by a pronounced lymphoid-neutrophilic infiltration of the tracheal and bronchial mucosa (signs of diffuse catarrhal inflammation of varying degrees and erosive deforming endobronchitis are verified), and in a complicated course with the presence of a purulent-inflammatory and erosive-hemorrhagic component with its vascularization and metaplastic changes and violations of the integrity of the epithelial lining also leads to a violation of the integrity of tissues due to destruction and necrosis. Hence, a method has been developed to stop bleeding in case of mucosal damage by local application of HEMOBEN, which allows us to quickly cover the bleeding surface with an adequate hemostatic effect.

Aerosolized Antibiotics to Manage Ventilator-Associated Infections: A Comprehensive Review.

Ventilator-associated lower respiratory tract infectious complications in critically ill patients cover a wide spectrum of one disease process (respiratory infection), initiating from tracheal tube and/or tracheobronchial colonization, to ventilator associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP). VAP occurence has been associated with increased intensive care unit (ICU) morbidity (ventilator days, as well as length of ICU and hospital stay) and ICU mortality. Therefore, treatments that aim at VAP/VAT incidence reduction are a high priority. The aim of the present review is to discuss the current literature concerning two major aspects: (a) can aerosolized antibiotics (AA) administered in a pre-emptive way prevent the occurrence of ventilator-associated infections? and (b) can VAT treatment with aerosolized avert the potential evolution to VAP? There were identified eight studies that provided data on the use of aerosolized antibiotics for the prevention of VAT/VAP. Most of them report favorable data on reducing the colonisation rate and the progression to VAP/VAT. Another four studies dealt with the treatment of VAT/VAP. The results support the decrease in the incidence to VAP transition and/or the improvement in signs and symptoms of VAP. Moreover, there are concise reports on higher cure rates and microbiological eradication in patients treated with aerosolized antibiotics. Yet, differences in the delivery modality adopted and resistance emergence issues preclude the generalisability of the results. Aerosolized antibiotic therapy can be used to manage ventilator-associated infections, especially those with difficult to treat resistance. The limited clinical data raise the need for large randomized controlled trials to confirm the benefits of AA and to evaluate the impact on antibiotic selection pressure.

Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19: a multinational, multicentre study, prospective, observational study

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40–2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98–1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

Nosocomial Infections in Adult Patients Supported by Extracorporeal Membrane Oxygenation in a Cardiac Intensive Care Unit.

The use of venoarterial (VA) extracorporeal membrane oxygenation therapy (ECMO) in patients admitted to cardiac intensive care units (CICU) has increased. Data regarding infections in this population are scarce. In this retrospective study, we analyzed the risk factors, outcome, and predictors of in-hospital mortality due to nosocomial infections in patients with ECMO admitted to a single coronary intensive care unit between July 2013 and March 2019 treated with VA-ECMO for >48 h. From 69 patients treated with VA-ECMO >48 h, (median age 58 years), 29 (42.0%) patients developed 34 episodes of infections with an infection rate of 0.92/1000 ECMO days. The most frequent were ventilator-associated pneumonia (57.6%), tracheobronchitis (9.1%), bloodstream infections (9.1%), skin and soft tissue infections (9.1%), and cytomegalovirus reactivation (9.1%). In-hospital mortality was 47.8%, but no association with nosocomial infections was found (p = 0.75). The number of days on ECMO (OR 1.14, 95% CI 1.01-1.30, p = 0.029) and noninfectious complications were higher in the infected patients (OR: 3.8 95% CI = 1.05-14.1). A higher baseline creatinine value (OR: 8.2 95% CI = 1.12-60.2) and higher blood lactate level at 4 h after ECMO initiation (OR: 2.0 95% CI = 1.23-3.29) were significant and independent risk factors for mortality. Conclusions: Nosocomial infections in medical patients treated with VA-ECMO are very frequent, mostly Gram-negative respiratory infections. Preventive measures could play an important role for these patients.

Ventilator-Associated Pneumonia in Immunosuppressed Patients.

Immunocompromised patients-including patients with cancer, hematological malignancies, solid organ transplants and individuals receiving immunosuppressive therapies for autoimmune diseases-account for an increasing proportion of critically-ill patients. While their prognosis has improved markedly in the last decades, they remain at increased risk of healthcare- and intensive care unit (ICU)-acquired infections. The most frequent of these are ventilator-associated lower respiratory tract infections (VA-LTRI), which include ventilator-associated pneumonia (VAP) and tracheobronchitis (VAT). Recent studies have shed light on some of the specific features of VAP and VAT in immunocompromised patients, which is the subject of this narrative review. Contrary to previous belief, the incidence of VAP and VAT might actually be lower in immunocompromised than non-immunocompromised patients. Further, the relationship between immunosuppression and the incidence of VAP and VAT related to multidrug-resistant (MDR) bacteria has also been challenged recently. Etiological diagnosis is essential to select the most appropriate treatment, and the role of invasive sampling, specifically bronchoscopy with bronchoalveolar lavage, as well as new molecular syndromic diagnostic tools will be discussed. While bacteria-especially gram negative bacteria-are the most commonly isolated pathogens in VAP and VAT, several opportunistic pathogens are a special concern among immunocompromised patients, and must be included in the diagnostic workup. Finally, the impact of immunosuppression on VAP and VAT outcomes will be examined in view of recent papers using improved statistical methodologies and treatment options-more specifically empirical antibiotic regimens-will be discussed in light of recent findings on the epidemiology of MDR bacteria in this population.